Benzamide compounds represented by sulpiride has been used as antischizophrenic drugs, and are well known to have less side effects on the extrapyramidal system and weak cataleptogenic activity unlike butyrophenone compounds such as haloperidol or phenothiazine compounds such as chlorpromazine. Sulpiride, however, is also reported to have a low bioavailability in oral administration and poor penetration across blood-brain barrier. Sulpiride is also used as anti-ulcer agents.
U.S. Pat. No. 3,527,761 or Journal of Medicinal Chemistry, Vol. 14, p. 1054 (1971) decribes 3-indoleethylamine compounds possessing mainly antihypertensive activity, and in particular, 3-{2-[4-(3-indolecarboxamido)-piperidino]ethyl}indole having antihypertensive and antihistaminic activities. Among these 3-indoleethylamine compounds, indoramin (INN, 3-[2-(4-benzamido-1-piperidyl)-ethyl]indole) is selected as the compound having stronger antihypertensive activity, and also exhibits antihistaminic activity and anticonvulsant activity. According to studies of the present inventors, indoramin shows weak apomorphine-antagonistic activity, but it cannot be used as neuroleptic and anxiolytic drugs because of exhibition of relatively strong antihypertensive activity. Other known 3-indoleethylamine compounds mentioned above do not show apomorphine-antagonistic activity, in practice.
Since benzamide compounds have dopamine-antagonistic activity as a main activity, the present inventors have synthesized a series of compounds in place of the phenyl moiety of the benzamide compounds into indole moiety which is the nucleus of serotonin, and investigated their pharmacological activities.